O-carboxymethyl chitosan/fucoidan nanoparticles increase cellular curcumin uptake

Abstract

Curcumin (Cur) is a polyphenolic compound extracted from turmeric (Curcuma longa), and exhibits several biological activities like antitumor, antioxidant, inhibiting cardiovascular diseases and inducing apoptosis. However, because of extremely low solubility and sensitivity to pH values, Cur is easily degradable in the gastrointestinal tract, resulting in reduced bioavailability. In this study, we developed pH-sensitive O-carboxymethyl chitosan/fucoidan (O-CMC/F) nanoparticles (NPs) for Cur delivery, and evaluated their physicochemical properties and influence on cells. Our results suggest that O-CMC and F reacted with calcium ions to obtain ionic crosslinked NPs of 100–200 nm. At a weight ratio of O-CMC to F of 1:1, the O-CMC/F NPs exhibited pH-sensitive properties. The Cur-loaded O-CMC/F NPs was 270 nm and encapsulated 92.8% Cur. Encapsulated Cur was stable in a simulated limosis pH environment (pH 2.5). However, in a simulated intestinal pH environment (pH 7.4), Cur was released from the O-CMC/F NPs. Encapsulated Cur was associated with considerably lower cytotoxicity to mouse fibroblasts cells (L929) than free Cur. When we used Caco-2 cells as an in vitro model to evaluate cellular uptake, we observed that the Cur-loaded O-CMC/F NPs were internalized by the cells through energy-dependent endocytic pathways. In conclusion, pH-sensitive O-CMC/F NPs effectively increase the cellular uptake of Cur and can potentially be used as carriers in oral delivery systems.